Title: Synthesis of novel antimitotic agents based on 2-amino-3-aroyl-5-(hetero)arylethynyl thiophene derivatives
Authors: Romagnoli, Romeo ×
Baraldi, Pier Giovanni
Cruz-Lopez, Olga
Tolomeo, Manlio
Cristina, Antonietta Di
Pipitone, Rosaria Maria
Grimaudo, Stefania
Balzarini, Jan
Brancale, Andrea
Hamel, Ernest #
Issue Date: May-2011
Publisher: Pergamon Press
Series Title: Bioorganic & Medicinal Chemistry Letters vol:21 issue:9 pages:2746-51
Abstract: Microtubules are dynamic structures that play a crucial role in cellular division and are recognized as an important target for cancer therapy. In search of new compounds with strong antiproliferative activity and simple molecular structure, a new series of 2-amino-3-(3',4',5'-trimethoxybenzoyl)-5-(hetero)aryl ethynyl thiophene derivatives was prepared by the Sonogashira coupling reaction of the corresponding 5-bromothiophenes with several (hetero)aryl acetylenes. When these compounds were analyzed in vitro for their inhibition of cell proliferation, the 2- and 3-thiophenyl acetylene derivatives were the most powerful compounds, both of which exerted cytostatic effects at submicromolar concentrations. In contrast, the presence of a more flexible ethyl chain between the (hetero)aryl and the 5-position of the thiophene ring resulted in significant reduction in activity relative to the 5-(hetero)aryl acetylene substituted derivatives. The effects of a selected series of compounds on cell cycle progression correlated well with their strong antiproliferative activity and inhibition of tubulin polymerization. We found that the antiproliferative effects of the most active compounds were associated with increase of the proportion of cells in the G(2)/M and sub-G(1) phases of the cell cycle.
ISSN: 0960-894X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
× corresponding author
# (joint) last author

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